Physical chemistry chemical physics : PCCP, Jan 14, 2006
We investigate the liquid structure, ion hydration, and some thermodynamic properties associated ... more We investigate the liquid structure, ion hydration, and some thermodynamic properties associated with the rigid geometry approximation to water by applying ab initio molecular dynamics simulations (AIMD) with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional at T = 320 K. We vary the rigid water geometry in order to locate a class of practical water models that yield reasonable liquid structure and dynamics, and to examine the progression of AIMD-predicted water behavior as the OH bond length varies. Water constrained at the optimal PBE gas phase geometry yields reasonable pair correlation functions. The predicted liquid phase pressure, however, is large ( approximately 8.0 kbar). Although the O-H bond in water should elongate when transferred from gas to the condensed phase, when it is constrained to 0.02, or even just 0.01 A longer than the optimal gas phase value, liquid water is predicted to be substantially overstructured compared to experiments. Zero temperature calculations of the thermodynamic properties of cubic ice underscore the sensitivity toward small variations in the O-H bond length. We examine the hydration structures of potassium, chloride, and formate ions in one rigid PBE water model. The results are in reasonable agreement with unconstrained AIMD simulations.
Journal of the American Chemical Society, Jan 13, 2008
The permeation, rejection, and transport of electrolytes in water-filled nanopores are critical t... more The permeation, rejection, and transport of electrolytes in water-filled nanopores are critical to ion current gating and desalination processes in synthetic porous membranes and the functions of biological ion channels. While the effects of confinement, pore polarizability, and ...
Journal of computational and theoretical nanoscience, 2009
We perform pressure-driven non-equilibrium molecular dynamics (MD) simulations to drive a 1.0 M N... more We perform pressure-driven non-equilibrium molecular dynamics (MD) simulations to drive a 1.0 M NaCl electrolyte through a dipole-lined smooth nanopore of diameter 12 Å penetrating a model membrane. We show that partial, about 70-80%, Cl(-) rejection is achieved at a ~68 atmosphere pressure. At the high water flux achieved in these model nanopores, which are particularly pertinent to atomistically smooth carbon nanotube membranes that permit fast water transport, the ion rejection ratio decreases with increasing water flux. The computed potential of mean force of Cl(-) frozen inside the nanopore reveals a barrier of 6.4 kcal/mol in 1.0 M NaCl solution. The Cl(-) permeation occurs despite the barrier, and this is identified as a dynamical effect, with ions carried along by the water flux. Na(+)-Cl(-) ion-pairing or aggregation near the pore entrance and inside the pore, where the dielectric screening is weaker than in bulk water, is critical to Cl(-) permeation. We also consider negative charges decorating the rim and the interior of the pore instead of dipoles, and find that, with sufficient pressure, Cl(-) from a 1.0 M NaCl solution readily passes through such nanopores.
We apply DFT+U-based ab initio molecular dynamics simulations to study the hydration structures o... more We apply DFT+U-based ab initio molecular dynamics simulations to study the hydration structures of U(III) and U(IV) ions, pertinent to redox reactions associated with uranium salts in aqueous media. U(III) is predicted to be coordinated to 8 water molecules, while U(IV) has a hydration number between 7 and 8. At least one of the innershell water molecules of the hydrated U(IV) complex becomes spontaneously deprotonated. As a result, the U(IV)-O pair correlation function exhibits a satellite peak at 2.15 Å associated with the shorter U(IV)-(OH(-)) bond. This feature is not accounted for in analysis of extended x-ray absorption fine structure and x-ray adsorption near edge structure measurements, which yield higher estimates of U(IV) hydration numbers. This suggests that it may be useful to include the effect of possible hydrolysis in future interpretation of experiments, especially when the experimental pH is close to the reported hydrolysis equilibrium constant value.
Quinone reductase 2 (NQO2) is an FAD-linked enzyme and the only known human target of two antimal... more Quinone reductase 2 (NQO2) is an FAD-linked enzyme and the only known human target of two antimalarial drugs, primaquine (PQ) and chloroquine (CQ). The structural differences between oxidized and reduced NQO2 and the structural basis for inhibition by PQ and CQ were investigated by x-ray crystallography. Structures of oxidized NQO2 in complex with PQ and CQ were solved at 1.4 Å resolution. CQ binds preferentially to reduced NQO2, and upon reduction of NQO2-CQ crystals, the space group changed from P2(1)2(1)2(1) to P2(1), with 1-Å decreases in all three unit cell dimensions. The change in crystal packing originated in the negative charge and 4-5º bend in the reduced isoalloxazine ring of FAD, which resulted in a new mode of CQ binding and closure of a flexible loop (Phe(126)-Leu(136)) over the active site. This first structure of a reduced quinone reductase shows that reduction of the FAD cofactor and binding of a specific inhibitor lead to global changes in NQO2 structure and is consistent with a functional role for NQO2 as a flavin redox switch.
Quinone reductase 2 (NQO2) exhibits off-target interactions with two protein kinase CK2 inhibitor... more Quinone reductase 2 (NQO2) exhibits off-target interactions with two protein kinase CK2 inhibitors, 4,5,6,7-1H-tetrabromobenzimidazole (TBBz) and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT). TBBz and DMAT induce apoptosis in cells expressing an inhibitor-resistant CK2, suggesting that the interaction with NQO2 may mediate some of their pharmacological effects. In this study, we have fully characterized the binding of TBBz and DMAT to NQO2. Fluorescence titrations showed that TBBz and DMAT bind oxidized NQO2 in the low nanomolar range; in the case of TBBz, the affinity for NQO2 was 40-fold greater than its affinity for CK2. A related CK2 inhibitor, 4,5,6,7-tetrabromobenzotriazole (TBB), which failed to cause apoptosis in cells expressing inhibitor-resistant CK2, binds NQO2 with an affinity 1000-fold lower than those of TBBz and DMAT. Kinetic analysis indicated that DMAT inhibits NQO2 by binding with similar affinities to the oxidized and reduced forms. Crystal structure analysis showed that DMAT binds reduced NQO2 in a manner different from that in the oxidized state. In oxidized NQO2, TBBz and DMAT are deeply buried in the active site and make direct hydrogen and halogen bonds to the enzyme. In reduced NQO2, DMAT occupies a more peripheral region and hydrogen and halogen bonds with the enzyme are mediated through three water molecules. Therefore, although TBB, TBBz, and DMAT are all potent inhibitors of CK2, they exhibit different activity profiles toward NQO2. We conclude that the active site of NQO2 is fundamentally different from the ATP binding site of CK2 and the inhibition of NQO2 by CK2 inhibitors is adventitious.
We apply first-principles density-functional calculations to study strain in dense amorphous tetr... more We apply first-principles density-functional calculations to study strain in dense amorphous tetrahedral carbon (a-tC). While the large strain present in small-ring structures, particularly three-member rings, could argue against their existence in a-tC, we demonstrate, based on energetic ...
We investigate the electron-hole interactions in spherical silicon nanocrystals by incorporating ... more We investigate the electron-hole interactions in spherical silicon nanocrystals by incorporating Coulomb, exchange, and spin-orbit couplings into a tight-binding model. We study the effect of the electron-hole attraction on the absorption spectra and on the dielectric constant, ...
The structural properties, energetics, and dynamics of Ca 2+ and Mn 2+ substituents in KTaO 3 are... more The structural properties, energetics, and dynamics of Ca 2+ and Mn 2+ substituents in KTaO 3 are investigated from first principles. It is found that Ca substitutes for both K and Ta ions. Oxygen vacancies bind to isolated Ca ions residing at Ta sites, causing off-center Ca ...
Physical chemistry chemical physics : PCCP, Jan 21, 2015
The applied potential governs lithium-intercalation and electrode passivation reactions in lithiu... more The applied potential governs lithium-intercalation and electrode passivation reactions in lithium ion batteries, but are challenging to calibrate in condensed phase DFT calculations. In this work, the "anode potential" of charge-neutral lithium-intercalated graphite (LiC6) with oxidized edge planes is computed as a function of Li-content (nLi) at edge planes, using ab initio molecular dynamics (AIMD), a previously introduced Li(+) transfer free energy method, and the experimental Li(+)/Li(s) value as reference. The voltage assignments are corroborated using explicit electron transfer from fluoroethylene carbonate radical anion markers. PF6(-) is shown to decompose electrochemically (i.e., not just thermally) at low potentials imposed by our voltage calibration technique. We demonstrate that excess electrons reside in localized states-in-the-gap in the organic carbonate liquid region, which is not semiconductor-like (band-state-like) as widely assumed in the literature.
Abstract. Current artificial immune system (AIS) classifiers have two major problems: (1) their p... more Abstract. Current artificial immune system (AIS) classifiers have two major problems: (1) their populations of B-cells can grow to huge proportions and (2) optimizing one B-cell (part of the classifier) at a time does not necessarily guar-antee that the B-cell pool (the whole ...
Physical chemistry chemical physics : PCCP, Jan 14, 2006
We investigate the liquid structure, ion hydration, and some thermodynamic properties associated ... more We investigate the liquid structure, ion hydration, and some thermodynamic properties associated with the rigid geometry approximation to water by applying ab initio molecular dynamics simulations (AIMD) with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional at T = 320 K. We vary the rigid water geometry in order to locate a class of practical water models that yield reasonable liquid structure and dynamics, and to examine the progression of AIMD-predicted water behavior as the OH bond length varies. Water constrained at the optimal PBE gas phase geometry yields reasonable pair correlation functions. The predicted liquid phase pressure, however, is large ( approximately 8.0 kbar). Although the O-H bond in water should elongate when transferred from gas to the condensed phase, when it is constrained to 0.02, or even just 0.01 A longer than the optimal gas phase value, liquid water is predicted to be substantially overstructured compared to experiments. Zero temperature calculations of the thermodynamic properties of cubic ice underscore the sensitivity toward small variations in the O-H bond length. We examine the hydration structures of potassium, chloride, and formate ions in one rigid PBE water model. The results are in reasonable agreement with unconstrained AIMD simulations.
Journal of the American Chemical Society, Jan 13, 2008
The permeation, rejection, and transport of electrolytes in water-filled nanopores are critical t... more The permeation, rejection, and transport of electrolytes in water-filled nanopores are critical to ion current gating and desalination processes in synthetic porous membranes and the functions of biological ion channels. While the effects of confinement, pore polarizability, and ...
Journal of computational and theoretical nanoscience, 2009
We perform pressure-driven non-equilibrium molecular dynamics (MD) simulations to drive a 1.0 M N... more We perform pressure-driven non-equilibrium molecular dynamics (MD) simulations to drive a 1.0 M NaCl electrolyte through a dipole-lined smooth nanopore of diameter 12 Å penetrating a model membrane. We show that partial, about 70-80%, Cl(-) rejection is achieved at a ~68 atmosphere pressure. At the high water flux achieved in these model nanopores, which are particularly pertinent to atomistically smooth carbon nanotube membranes that permit fast water transport, the ion rejection ratio decreases with increasing water flux. The computed potential of mean force of Cl(-) frozen inside the nanopore reveals a barrier of 6.4 kcal/mol in 1.0 M NaCl solution. The Cl(-) permeation occurs despite the barrier, and this is identified as a dynamical effect, with ions carried along by the water flux. Na(+)-Cl(-) ion-pairing or aggregation near the pore entrance and inside the pore, where the dielectric screening is weaker than in bulk water, is critical to Cl(-) permeation. We also consider negative charges decorating the rim and the interior of the pore instead of dipoles, and find that, with sufficient pressure, Cl(-) from a 1.0 M NaCl solution readily passes through such nanopores.
We apply DFT+U-based ab initio molecular dynamics simulations to study the hydration structures o... more We apply DFT+U-based ab initio molecular dynamics simulations to study the hydration structures of U(III) and U(IV) ions, pertinent to redox reactions associated with uranium salts in aqueous media. U(III) is predicted to be coordinated to 8 water molecules, while U(IV) has a hydration number between 7 and 8. At least one of the innershell water molecules of the hydrated U(IV) complex becomes spontaneously deprotonated. As a result, the U(IV)-O pair correlation function exhibits a satellite peak at 2.15 Å associated with the shorter U(IV)-(OH(-)) bond. This feature is not accounted for in analysis of extended x-ray absorption fine structure and x-ray adsorption near edge structure measurements, which yield higher estimates of U(IV) hydration numbers. This suggests that it may be useful to include the effect of possible hydrolysis in future interpretation of experiments, especially when the experimental pH is close to the reported hydrolysis equilibrium constant value.
Quinone reductase 2 (NQO2) is an FAD-linked enzyme and the only known human target of two antimal... more Quinone reductase 2 (NQO2) is an FAD-linked enzyme and the only known human target of two antimalarial drugs, primaquine (PQ) and chloroquine (CQ). The structural differences between oxidized and reduced NQO2 and the structural basis for inhibition by PQ and CQ were investigated by x-ray crystallography. Structures of oxidized NQO2 in complex with PQ and CQ were solved at 1.4 Å resolution. CQ binds preferentially to reduced NQO2, and upon reduction of NQO2-CQ crystals, the space group changed from P2(1)2(1)2(1) to P2(1), with 1-Å decreases in all three unit cell dimensions. The change in crystal packing originated in the negative charge and 4-5º bend in the reduced isoalloxazine ring of FAD, which resulted in a new mode of CQ binding and closure of a flexible loop (Phe(126)-Leu(136)) over the active site. This first structure of a reduced quinone reductase shows that reduction of the FAD cofactor and binding of a specific inhibitor lead to global changes in NQO2 structure and is consistent with a functional role for NQO2 as a flavin redox switch.
Quinone reductase 2 (NQO2) exhibits off-target interactions with two protein kinase CK2 inhibitor... more Quinone reductase 2 (NQO2) exhibits off-target interactions with two protein kinase CK2 inhibitors, 4,5,6,7-1H-tetrabromobenzimidazole (TBBz) and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT). TBBz and DMAT induce apoptosis in cells expressing an inhibitor-resistant CK2, suggesting that the interaction with NQO2 may mediate some of their pharmacological effects. In this study, we have fully characterized the binding of TBBz and DMAT to NQO2. Fluorescence titrations showed that TBBz and DMAT bind oxidized NQO2 in the low nanomolar range; in the case of TBBz, the affinity for NQO2 was 40-fold greater than its affinity for CK2. A related CK2 inhibitor, 4,5,6,7-tetrabromobenzotriazole (TBB), which failed to cause apoptosis in cells expressing inhibitor-resistant CK2, binds NQO2 with an affinity 1000-fold lower than those of TBBz and DMAT. Kinetic analysis indicated that DMAT inhibits NQO2 by binding with similar affinities to the oxidized and reduced forms. Crystal structure analysis showed that DMAT binds reduced NQO2 in a manner different from that in the oxidized state. In oxidized NQO2, TBBz and DMAT are deeply buried in the active site and make direct hydrogen and halogen bonds to the enzyme. In reduced NQO2, DMAT occupies a more peripheral region and hydrogen and halogen bonds with the enzyme are mediated through three water molecules. Therefore, although TBB, TBBz, and DMAT are all potent inhibitors of CK2, they exhibit different activity profiles toward NQO2. We conclude that the active site of NQO2 is fundamentally different from the ATP binding site of CK2 and the inhibition of NQO2 by CK2 inhibitors is adventitious.
We apply first-principles density-functional calculations to study strain in dense amorphous tetr... more We apply first-principles density-functional calculations to study strain in dense amorphous tetrahedral carbon (a-tC). While the large strain present in small-ring structures, particularly three-member rings, could argue against their existence in a-tC, we demonstrate, based on energetic ...
We investigate the electron-hole interactions in spherical silicon nanocrystals by incorporating ... more We investigate the electron-hole interactions in spherical silicon nanocrystals by incorporating Coulomb, exchange, and spin-orbit couplings into a tight-binding model. We study the effect of the electron-hole attraction on the absorption spectra and on the dielectric constant, ...
The structural properties, energetics, and dynamics of Ca 2+ and Mn 2+ substituents in KTaO 3 are... more The structural properties, energetics, and dynamics of Ca 2+ and Mn 2+ substituents in KTaO 3 are investigated from first principles. It is found that Ca substitutes for both K and Ta ions. Oxygen vacancies bind to isolated Ca ions residing at Ta sites, causing off-center Ca ...
Physical chemistry chemical physics : PCCP, Jan 21, 2015
The applied potential governs lithium-intercalation and electrode passivation reactions in lithiu... more The applied potential governs lithium-intercalation and electrode passivation reactions in lithium ion batteries, but are challenging to calibrate in condensed phase DFT calculations. In this work, the "anode potential" of charge-neutral lithium-intercalated graphite (LiC6) with oxidized edge planes is computed as a function of Li-content (nLi) at edge planes, using ab initio molecular dynamics (AIMD), a previously introduced Li(+) transfer free energy method, and the experimental Li(+)/Li(s) value as reference. The voltage assignments are corroborated using explicit electron transfer from fluoroethylene carbonate radical anion markers. PF6(-) is shown to decompose electrochemically (i.e., not just thermally) at low potentials imposed by our voltage calibration technique. We demonstrate that excess electrons reside in localized states-in-the-gap in the organic carbonate liquid region, which is not semiconductor-like (band-state-like) as widely assumed in the literature.
Abstract. Current artificial immune system (AIS) classifiers have two major problems: (1) their p... more Abstract. Current artificial immune system (AIS) classifiers have two major problems: (1) their populations of B-cells can grow to huge proportions and (2) optimizing one B-cell (part of the classifier) at a time does not necessarily guar-antee that the B-cell pool (the whole ...
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